IL37976A - Crystalline hydrate of trisodium d-fructose-1,6-diphosphoric acid and process for the preparation thereof - Google Patents

Description

CRYSTALLINE HYDRATE OF TRIS DIUM ACID AND PROCESS FOR THE PREPARATION The present invention is concerned with a crystalline hydrate of acid a process for the preparation acid was first isolated by Young in especially in the form of its sodium is used pharmaceutically in the treatment of various metabolic Although the sodium salt of diphosphoric acid has been known a long time and is prepared on a large it ha3 hitherto never been possible to convert the salt into a crystallised in the case of the known production a solution of sodium acid is obtained in the laet hitherto the compound has had to be converted into a solid form by processes such as precipitation with organic spray drying or freeze the amorphous product obtained by any of the known processes is extremely hygroscopic and becomes lumpy or deliquesces in the Due to these properties of the considerable difficulties arise during despatch and working especially galenical preparations are to be made in solid we now found under certain the trisodium salt of diphosphoric acid can be crystallised as the the present invention provides crystalline sodium acid octahydrate as a new The trisodium acid according to the present invention is in the form of inonoclinic crystals of the spatial group with the cell dimensions a and c and angle β The crystalline octahydrate according to the present invention is no longer hygroscopic in comparison with the previously known amorphous has a considerably greater According to the present there is also provided a process the preparation of crystalline trisodium acid wherein a dilute aqueous solution of diphosphoric acid in the form its sodium salt is adjusted to a value between and preferably between mixed at 15 to with a lower alkanol until the commencement of turbidity cooled until crystal formation mixed further alkanol in an amount of up to 2 to 3 times the volume of the initial aqueous solution and the crystal formation completed at a reduced The aqueous starting solution used preferably has a content of trisodium acid of about 7 to The pH value of the initial aqueous solution is preferably adjusted with a sodium hydroxide solution with an the sodium salt of which has at least a certain degree of solubility in the alkanol A preferred acid for this purpose for acetic After adjustment of the pH the solution if clarified by By lower according to the present invention there is to be understood an alkanol containing up to 3 carbon ethanol being it is possible to use or isopropanol in the case of the latter crystal formation is less the yield is lower and the product obtained sometimes contains and thus hygroscopi The alkanol is preferably added at ambient temperatu until a slight turbidity The solution is then slowly further cooled until the commencement of crystallis ation can be As soon as the first visible crystals are further alkanol is preferably up to a fold volume of referred to the initia volume of the aqueous For completion of the the solution is further for example by placing in a ref igerato In the case of a temperature of about and with the us of a fold volume of crystallisation is ended after 20 to o The crystalline product can be separated by the usual physical then washed with alcohol and The mother liquor at to of the sodium salt initially When temperatures above are preferably avoided in order to prevent the loss of water of crystalli ation or a destruction of the crystal Drying agents which vigorously remove for phosphorus are preferably also not accompanying photographs Λ and B show the crysta The following Example is given for the purpose of illustrating the present Example 100 amorphous trisodium acid are dissolved in 900 distilled The pH value of the solution is adjusted to the addition of acetic acid and then filtered through a Ethanol is now added in a thin stream until turbidity can be This is the case after the addition of about 700 The solution is placed in a refrigerator of After crystallisation A 800 alcohol are then with After the crystal slurry which in the formed is off with suction the crystals are stirred up with 500 again ltered with suction and then dried in a vacuum drying cabinet at without the use of a drying There are trisodium diphosphoric acid In the mother 6 of the trisodium can be detected Properties of the Sum Melting point Molecular weight t found enzymatically sodium found water found phosphorus optical rotation water cryatallographic crystal system monoclin spatial group 21 cell dimensions a c angle 157 insufficientOCRQuality

Claims (10)

What we claim is :~

1. Ci'ystalline trisodium • acid octahydrate.

2. . Crystals according to crystals of spatial group P , b = 11.651 and c = 7.1 £ and angle /? = 108°.

3. Process for the preparation of crystals according to claim , wherein a dilute aqueous solution of D-fructose- the initial aqueous solution and the crystal formation completed at a reduced temperature.

4. Process according to claim 3, wherein" the initial aqueous solution is adjusted to a pH of 5.9;.to 6.1.

5. Process according to claim 3 or k, wherein the pH value of the initial aqueous solution is adjusted with sodium hydroxide solution or with an acid, the sodium salt of which is soluble in the alkanol used.

6. Process according to any of claims 3 - 5, wherein the initial aqueous solution contains 7 to 13 of D- fructose- ,6-diphosphoric acid sodium salt.

7. Process according to any of claims 3 - 6, wherein the lower alkanol used is ethanol.

8. Process according to any of claims 3 - 7, wherein the further alkanol is added in an amount of up to 1,5 times the volume, referred to the volume of the initial aqueous solution.

9. ' Process for the preparation of crystals according to claim 1 , substantially as hereinbefore described and exemplif ed.

10. / .Crystalline tri sodium D-fructose-1 ,6-diphosphoric acid octahydrate, whenever prepared by the process according to any of claims 3 ~ 9. Attorney for Applicants